Nell L J, McCammon J A, Subramaniam S
Chemistry Department, University of Houston, Texas 77204-5641.
Biopolymers. 1992 Jan;32(1):11-21. doi: 10.1002/bip.360320104.
A knowledge-based three-dimensional model of an anti-insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL-5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL-5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL-5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125.
利用在其他已知晶体学免疫球蛋白中发现的保守残基结构，构建了抗胰岛素抗体125的基于知识的三维模型。使用QUANTA和CHARMm软件，在硅图4D70GT工作站上对125个氨基酸序列进行了分子建模和力学分析。通过使用抗体HyHEL-5的晶体学坐标进行支架搭建，构建了一个最小模型，因为它与125具有最高的氨基酸序列同源性（轻链84%，重链65%）。对125中比HyHEL-5更长的三个高变环转角（L1、L3和H3）分别进行建模，并将其纳入HyHEL-5结构中；然后进行其他氨基酸替换并优化扭转。125模型保留了抗体的所有结构属性以及已知抗体中保守的结构。尽管该位点有许多极性氨基酸（尤其是丝氨酸），但整体范德华表面形状由芳香族侧链的位置决定。基于该模型，有人提出氢键可能是人类胰岛素A链环抗原表位与125之间相互作用的关键。
